Atherosclerotic cardiovascular disease is the leading cause of death in developed nations. Traditional risk factors predict atherosclerotic disease in populations but lack specificity in predicting atherosclerosis severity in individuals.
Since modifiable risk factors account for most myocardial infarctions worldwide, early and accurate identification of high-risk individuals would allow better targeting of aggressive preventive strategies. Yusuf S, Hawken S, Ounpuu S, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet 2004; 364:937-52. The incidence of coronary heart disease can be predicted in populations based on traditional risk factors [Wilson P W, D'Agostino R B, Levy D, Belanger A M, Silbershatz H, Kannel W B. Prediction of coronary heart disease using risk factor categories. Circulation 1998; 97:1837-47], but these factors lack specificity in predicting severity of atherosclerosis and likelihood of cardiovascular events in individuals [Greenland P, LaBree L, Azen S P, Doherty T M, Detrano R C. Coronary artery calcium score combined with Framingham score for risk prediction in asymptomatic individuals. Jama 2004; 291:210-5; Desai M Y, Nasir K, Braunstein J B, et al. Underlying risk factors incrementally add to the standard risk estimate in detecting subclinical atherosclerosis in low- and intermediate-risk middle-aged asymptomatic individuals. Am Heart J 2004; 148:871-7]. Consequently, other noninvasive methods are needed beyond traditional risk factors for early and accurate identification of individuals at high risk for atherosclerosis.
As is known to those skilled in the art, abnormalities of two arterial properties—endothelial function and central arterial stiffness—are associated with increased risk of atherosclerosis and cardiovascular events [Schroeder S, Enderle M D, Ossen R, et al. Noninvasive determination of endothelium-mediated vasodilation as a screening test for coronary artery disease: pilot study to assess the predictive value in comparison with angina pectoris, exercise electrocardiography, and myocardial perfusion imaging. Am Heart J 1999; 138:731-9; Neunteufl T, Katzenschlager R, Hassan A, et al. Systemic endothelial dysfunction is related to the extent and severity of coronary artery disease. Atherosclerosis 1997; 129:111-8; Teragawa H, Kato M, Kurokawa J, Yamagata T, Matsuura H, Chayama K. Usefulness of flow-mediated dilation of the brachial artery and/or the intima-media thickness of the carotid artery in predicting coronary narrowing in patients suspected of having coronary artery disease. Am J Cardiol 2001; 88:1147-51; Oliver J J, Webb D J. Noninvasive assessment of arterial stiffness and risk of atherosclerotic events. Arterioscler Thromb Vase Biol 2003; 23:554-66; Sutton-Tyrrell K, Najjar S S, Boudreau R M, et al. Elevated aortic pulse wave velocity, a marker of arterial stiffness, predicts cardiovascular events in well-functioning older adults. Circulation 2005; 111:3384-90].
Furthermore, endothelial dysfunction and increased central arterial stiffness precede atherosclerosis by years or even decades [Celermajer D S, Sorensen K E, Gooch V M, et al. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet 1992; 340:1111-5; Iannuzzi A, Licenziati M R, Acampora C, et al. Preclinical changes in the mechanical properties of abdominal aorta in obese children. Metabolism 2004; 53:1243-6; Wildman R P, Mackey R H, Bostom A, Thompson T, Sutton-Tyrrell K. Measures of obesity are associated with vascular stiffness in young and older adults. Hypertension 2003; 42:468-73].
Hence, there is much interest in developing noninvasive techniques for assessing endothelial function and/or central arterial stiffness in order to enhance cardiovascular risk stratification [Taylor A J, Merz C N, Udelson J E. 34th Bethesda Conference: Executive summary—can atherosclerosis imaging techniques improve the detection of patients at risk for ischemic heart disease? J Am Coll Cardiol 2003; 41:1860-2; Corretti M C, Plotnick G D, Vogel R A. Technical aspects of evaluating brachial artery vasodilatation using high-frequency ultrasound. Am J Physiol 1995; 268:H1397-404; Kuvin J T, Patel A R, Sliney K A, et al. Peripheral vascular endothelial function testing as a noninvasive indicator of coronary artery disease. J Am Coll Cardiol 2001; 38:1843-9; Moens A L, Goovaerts I, Claeys M J, Vrints C J. Flow-mediated vasodilation: a diagnostic instrument, or an experimental tool? Chest 2005; 127:2254-63]. Thus, evaluating either or both of these arterial properties may enable early and accurate identification of high-risk individuals.
A standard approach to assessing central arterial stiffness is to measure central pulse wave velocity—pulse waves travel faster in stiffer arteries. There are two particular methods of assessing central pulse wave velocity that typically measure transit time between two different aortic sites [Mohiaddin R H, Firmin D N, Longmore D B. Age-related changes of human aortic flow wave velocity measured noninvasively by magnetic resonance imaging. J Appl Physiol 1993; 74:492-7; Rogers W J, Hu Y L, Coast D, et al. Age-associated changes in regional aortic pulse wave velocity. J Am Coll Cardiol 2001; 38:1123-9] or two peripheral arterial sites [Davies J I, Struthers A D. Pulse wave analysis and pulse wave velocity: a critical review of their strengths and weaknesses. J Hypertens 2003; 21:463-72].
When assessing central pulse wave velocity by measuring transit time between two different aortic sites, the aorta—the major artery in the chest—is imaged using MRI and the arrival time of the pulse wave at two or more aortic locations is determined. The distance between each of two points is typically determined using the acquired image and the pulse wave velocity is determined using the difference between the arrival times at two locations and the distance between these two points (i.e., Vpw=distance/time, where the distance and time is that between the two locations). This particular methodology can involve breath-holding and can involve time-consuming scanning and data analysis.
In the other methodology where two peripheral sites are used, the difference in pulse-wave arrival times at two different peripheral arterial locations, such as the radial and femoral arteries is determined. Also, the distance between these two peripheral arterial locations is determined. In the common technique often called applanation tonometry, two transducer or sensors are located external to the body and in proximity to the peripheral arterial locations. The transducers can be used to generate a time history of pressure changes and thereby sense the arrival of a pulse wave. The distance between these two peripheral arterial locations is typically determined by extending a tape measurer between the locations of the two sensors.
As indicated above, vascular physiology can be assessed, in part, through measurements of endothelial function. Changes in the diameter of an artery in response to a stimulus such as change in blood flow velocity through the artery (arterial wall shear stress, WSS) are indicative of endothelial function, known as flow mediated dilation (FMD). Endothelial function can be measured by inflating a blood pressure cuff around a subject's arm and monitoring velocity of blood flowing through a brachial artery while measuring the artery's diameter before, during and after the inflation of the cuff.
Vascular endothelium, the inner lining of blood vessels, is crucially important to maintaining vascular health. Endothelial cells regulate thrombosis, inflammation, vasomotion, and cell proliferation through the synthesis and release of substances including nitric oxide and endothelin-1. Cardiovascular risk factors are associated with endothelial dysfunction, and agents that reduce cardiovascular risk also improve endothelial function. Hence, endothelial dysfunction is considered to be an important common pathway by which risk factors promote atherosclerosis. Furthermore, endothelial dysfunction is associated with coronary events. Consequently, there is much interest in assessing endothelial function non-invasively.
It thus would be desirable to provide new non-invasive methods for assessing central arterial stiffness using a non-invasive imaging technique such as Magnetic Resonance Imaging (MRI) as well as applications programs embodying such methods. It would be particularly desirable to provide such methods that would assess central arterial stiffness by use of image data acquired at a single peripheral arterial location such as for example, the femoral artery. It also would be desirable to provide new non-invasive methods whereby one acquires image data to assess one or more vascular properties, such as central arterial stiffness, local arterial stiffness and/or vasculature reactivity using a non-invasive technique (e.g., MRI) at a single peripheral arterial location such as for example, the femoral artery, as well as applications programs embodying such methods. Such a method would be particularly adaptable so that the image data for these one or more vascular properties is obtained without having to reposition or relocate the detector or imaging coil used to acquire the image data.
The references referred to herein and discussed herein are provided solely for their disclosure prior to the filing date of the present application. Nothing herein is to be construed as an admission that the inventors are not entitled to antedate such disclosure by virtue of prior invention.